Overexpression of TRPM7 promotes the therapeutic effect of curcumin in wound healing through the STAT3/SMAD3 signaling pathway in human fibroblasts

Abstract

ObjectiveCurcumin, a natural extract from the rhizomes of Curcuma longa, is also known as a curcuminoid. Curcumin has been studied as a therapeutic drug for wound healing because of its anti-inflammatory, anti-oxidant, and anti-bacterial activities. However, the detailed mechanism of curcumin in wound healing is not clear. It is well-known that the skin is the largest organ in humans and prevents tissues from damage, including infection, radiation, and mechanical damage. Wound healing of the skin is a complex physiological regulation process requiring various cell types and cytokines; hence, wound healing, including surgery and care, incurs a huge expenditure each year. Transient receptor potential cation channel subfamily M member 7 (TRPM7) regulates multiple physiological and pharmacological processes through its channel and kinase activities. In addition, TRPM7 regulates cell adhesion, migration, and anti-oxidative activity, thereby playing a regulatory role in the wound healing process. This study aimed to explore the function of curcumin in the wound healing process. Methods: We first established TRPM7 overexpression and knockdown models in fibroblasts using lentivirus. CCK-8 and wound healing assays were used to clarify whether overexpression of TRPM7 promoted proliferation and migration in fibroblasts. Expression of target genes and proteins was detected using qPCR and western blotting. Concentrations of migration-related cytokines were measured using ELISA. Results: Proliferation and migration of fibroblasts increased after curcumin treatment and was further enhanced after overexpression of TRPM7. In addition, expression of proliferation-related genes and proteins was elevated after TRPM7 overexpression. Further, the secretion of migration-related cytokines was elevated after TRPM7 overexpression. Conclusion: Curcumin treatment promoted proliferation and migration of fibroblasts, and these effects were mediated by the signal transducer and activator of transcription 3 (STAT3)/SMAD family member 3/hypoxia-inducible factor 1 subunit alpha signaling pathway. Thus, we conclude that overexpression of TRPM7 might contribute to wound healing.